The regional cerebral metabolic rate for glucose (rCMRglc) was examined as a measure of cerebral functional activity in 49 healthy men between the ages of 21 and 83 years, by means of positron emission tomography (PET). Average hemispheric glucose utilization in individual regions of the right and left hemispheres did not decline significantly with age (p greater than 0.05), even after correction for cerebral atrophy. Asymmetry of cerebral metabolism in mildly and moderately demented Alzheimer's disease patients was shown to be unchanged and correlated with appropriate neuropsychological deficits over periods of up to 2 years. No significant relation between age at onset of dementia and neuropsychologic manifestations of AD was found when early and late onset patients were compared, although early onset patients had more severe parietal lobe hypometabolism. Longitudinal analysis of mildly demented patients demonstrated a systematic progression of neuropsychological deficits which were preceded by metabolic abnormalities by many months. Using a linear histogram method, ratios of peak rCMRglc in association cortex to peak rCMRglc in primary cortex were significantly reduced in mild and moderate- severe AD patients. These ratios also correlated significantly with dementia severity. Regional cerebral metabolism was reduced in older as compared to younger adults with Down syndrome, as expected from the Alzheimer-type neuropathology in older Down subjects. Similarities between Alzheimer's disease and dementia and cognitive deterioration in Down syndrome were demonstrated.